Caspase-11 is a key regulator of proinflammatory cytokine IL1b maturation and pathological apoptosis. Caspase-11 is not expressed in most tissues under normal condition, but highly inducible upon pathological stimulation such as in the presence of lipopolysaccharide (LPS). Here, we describe the identification and characterization of wedelolactone, a natural compound that inhibits LPS-induced caspase-11 expression in cultured cells by inhibiting NF-jB-mediated transcription. We demonstrate that wedelolactone is an inhibitor of IKK, a kinase critical for activation of NF-jB by mediating phosphorylation and degradation of IjBa.
Studies on nasal T/natural killer (NK)-cell lymphoma have been hampered by its tendency to cause necrosis. Thus, the establishment of cell lines of this neoplasm would seem to be valuable. This study attempted to establish cell lines from primary lesions of this tumor, and successfully obtained 2 novel Epstein-Barr virus (EBV)-positive cell lines, SNK-6 and SNT-8, by means of highdose recombinant interleukin 2. Flow cytometry showed that SNK-6 had an NK-cell phenotype, CD3 ؊ CD4 ؊ CD8 ؊ CD19 ؊ CD56 ؉ Tcell receptor (TCR) ␣/ ؊ TCR ␥/␦ ؊ , whereas SNT-8 was CD3 ؉ CD4 ؊ CD8 ؊ CD19 ؊ CD56 ؉ TCR ␣/ ؊ TCR ␥/␦ ؉ . These were consistent with immunophenotypes of their original tumors, and the cell lines had monoclonal EBV clones identical to ones in their original tumors. Thus, the cell lines developed from cells forming the primary lesions. Genotypic analysis showed that SNK-6 had unrearranged TCR and immunoglobulin heavy-chain genes, supporting the conclusion that SNK-6 was of NK-cell lineage. On the other hand, SNT-8 had rearranged TCR -, ␥-, and ␦-chain genes, and together with its phenotype, SNT-8 proved to be a ␥␦ T-cell line. This is the first report of the establishment of cell lines from primary lesions of nasal T/NK cell lymphomas, and the results demonstrated that there are at least 2 lineages, NK-and ␥␦ T-cell, in this neoplasm. Moreover, it has been suggested that nasal T/NK cell lymphomas of these lineages may belong to the same clinicopathologic entity because both types of cases shared common clinical and histopathologic features. IntroductionNasal T/natural killer (NK)-cell lymphoma is a distinct clinicopathologic entity characterized by progressive necrotic lesions in the nasal cavity, nasopharynx, and palate. 1 It has been called angiocentric lymphoma, lethal midline granuloma, or polymorphic reticulosis. 2 It is a relatively rare disease associated with a poor prognosis and more often seen in Asia than in the United States and Europe. 3-14 Nasal T/NK-cell lymphomas can exhibit a broad histologic spectrum and usually show invasion of the vascular walls, which is associated with prominent ischemic necrosis of both tumor cells and normal tissue.The most characteristic feature of the disease is a consistent and strong association with the Epstein-Barr virus (EBV); indeed, almost all cases are positive for EBV irrespective of ethnic difference, [15][16][17][18][19][20][21][22] yet the precise role of the virus in the etiology of the disease is poorly understood. The cellular origin of the nasal T/NK-cell lymphoma has been controversial. It was initially thought to originate from the T-cell lineage based on immunophenotype. [23][24][25][26][27] Later studies using combined immunophenotypic and genotypic analysis have suggested that most nasal T/NK-cell lymphomas are of NK-cell lineage, being CD56 ϩ , negative for surface CD3 (Leu4), and unassociated with rearrangements of the T-cell receptor (TCR) genes. 11,[28][29][30] On the other hand, some studies have reported the existence of T-cell lymphomas that...
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